Bipolar patients' brain cells predict response to lithium

Bipolar disorder affects more than five million Americans and is often a challenge to treat. If patients’ severe mood swings aren’t helped with lithium, doctors often piece together treatment plans with antipsychotic drugs, antidepressants and mood stabilizers. But they often help only the depressive swings of bipolar or the opposing manic swings, not both.

To study the underlying cause of bipolar disorder researchers collected skin cells from six bipolar patients, reprogrammed the cells to become stem cells, and then coaxed the stem cells to develop into neurons. They then compared those neurons to ones from healthy people.

The brain cells of patients with bipolar disorder, characterized by severe swings between depression and elation, are more sensitive to stimuli than other people’s brain cells, researchers have discovered.

“The cells we have from all six patients are much more sensitive in that you don’t need to activate them very strongly to see a response.” And the mitochondria–energy-generating powerhouses–inside the cells were also more active, says the author.

Surprisingly–although neurons from the two groups of patients had seemed identical (and equally sensitive) in the first tests–they behaved differently when exposed to the lithium. Cells from lithium responder patients showed weakened excitability after growing in the lithium. But cells from patients who hadn’t been helped by the drug remained hyperexcitable.

The findings don’t yet explain why lithium works for some patients and not others, but offers a starting point to probe what the differences between the cells are. And the bipolar neurons also offer a platform to ask other questions about biopolar disorder.